Bromoacetic Acid → 2-[5-{[(4-Chlorobenzyl)amino]carbonyl}-2-(3-hydroxy-1-propynyl)4-oxothieno[2,3-b]pyridin-7(4H)-yl]acetic Acid

HRID 1978944Notes

Reaction equation

[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:23])=[C:12]3[CH:18]=[C:17]([C:19]#[C:20][CH2:21][OH:22])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:33][C:34]([OH:36])=[O:35]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[CH:18]=[C:17]([C:19]#[C:20][CH2:21][OH:22])[S:16][C:13]=3[N:14]([CH2:33][C:34]([OH:36])=[O:35])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of N-(4-chlorobenzyl)-4-hydroxy-2-(3-hydroxy-1-propynyl)-thieno[2,3-b]pyridine-5-carboxamide (Example No. 5) (0.250 g) in DMF (3 mL) is added K2CO3 (0.278 g) and bromoacetic acid (0.279 g). The reaction is heated to 100° C. and stirred for 18 h. An additional 0.200 g of bromoacetic acid is added and the reaction is stirred for an additional 18 h. The reaction mixture is concentrated in vacuo, and the resulting residue is dissolved in 10% NaOH and washed with CH2Cl2. The aqueous layer is acidified with conc. HCl and the resulting precipitate is filtered. This material is recrystallized 3 times from methanol to yield 0.068 g (24%) of the title compound as a tan solid.

Workup

stirringthe reaction is stirred for an additional 18 h
concentrationThe reaction mixture is concentrated in vacuo
dissolutionthe resulting residue is dissolved in 10% NaOH
washwashed with CH2Cl2
filtrationthe resulting precipitate is filtered
customThis material is recrystallized 3 times from methanol

Sources & evidence

ORD record: ord-3421db6cf4a3454087c8f0eadb220fe3
Source dataset: uspto-grants-2001_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06239142B1

Reaction notes

Loading…